Singapore Immunology Network (SIgN), A*STAR, Biopolis, Singapore, Singapore.
Genomics of the Innate Immune System Unit, San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Nat Rev Immunol. 2019 Apr;19(4):255-265. doi: 10.1038/s41577-019-0141-8.
Structured models of ontogenic, phenotypic and functional diversity have been instrumental for a renewed understanding of the biology of immune cells, such as macrophages and lymphoid cells. However, there are no established models that can be used to define the diversity of neutrophils, the most abundant myeloid cells. This lack of an established model is largely due to the uniquely short lives of neutrophils, a consequence of their inability to divide once terminally differentiated, which has been perceived as a roadblock to functional diversity. This perception is rapidly evolving as multiple phenotypic and functional variants of neutrophils have been found, both in homeostatic and disease conditions. In this Opinion article, we present an overview of neutrophil heterogeneity and discuss possible mechanisms of diversification, including genomic regulation. We suggest that neutrophil heterogeneity is an important feature of immune pathophysiology, such that co-option of the mechanisms of diversification by cancer or other disorders contributes to disease progression.
成体发生、表型和功能多样性的结构模型对于重新理解免疫细胞（如巨噬细胞和淋巴细胞）的生物学特性至关重要。然而，目前还没有可用于定义中性粒细胞（最丰富的髓样细胞）多样性的既定模型。缺乏这样的模型在很大程度上是由于中性粒细胞独特的短暂寿命，这是由于它们一旦终末分化就无法分裂的结果，这被认为是功能多样性的一个障碍。这种看法正在迅速改变，因为已经在稳态和疾病条件下发现了多种中性粒细胞的表型和功能变体。在这篇观点文章中，我们概述了中性粒细胞的异质性，并讨论了多样化的可能机制，包括基因组调控。我们认为，中性粒细胞的异质性是免疫病理生理学的一个重要特征，因此癌症或其他疾病通过多样化机制的选择有助于疾病的进展。
